Dialysis modality and delayed graft function after cadaveric renal transplantation

The purpose of this investigation was to compare outcomes in the immediate posttransplant period for hemodialysis (HD) and peritoneal (PD) dialysis patients who received cadaveric renal transplantation. Data were obtained from the United Network of Organ Sharing on all cadaveric graft recipients who were dialysis-dependent at the time of transplantation between April 1994 and December 1995. Baseline characteristics were compared between groups, and multivariate logistic regression was performed with outcome measures including urine production in the first 24 h posttransplantation (U24), requirement for dialysis in the first week posttransplant (FWDIAL), and treatment for acute rejection during the initial hospitalization. The odds of oliguria (not producing urine in the first 24 h) were 1.49 (1.28 to 1.74) times higher in HD versus PD patients. After adjustment for other comorbid conditions including age, gender, race, HLA mismatch, time on dialysis, panel-reactive antibodies, and cold and warm ischemia time, the odds of oliguria were 1.60 (1.14 to 2.25) times higher in black HD patients compared with PD patients and 1.29 (1.06 to 1.57) times higher in white HD patients. In a similar manner, after adjustment for significant comorbid conditions, the odds of requiring dialysis in the first week were 1.56 (1.22 to 2.0) times higher in black HD patients versus PD patients and 1.40 (1.21 to 1.60) times higher in white HD patients. The rate of acute rejection was similar during the first hospitalization. These results suggest that there is an association between hemodialysis and delayed graft function. Differences in biocompatibility between the two modalities could potentially be responsible.     

Ventilation and gas exchange in patients with chronic renal failure treated with hemodialysis (HD) and intermittent peritoneal dialysis (IPD)

In 18 patients with chronic renal failure treated by hemodialysis (HD) before, during and after dialysis procedure breathing patterns and blood gases were estimated. Significant changes in PdCO2 and PvCO2 during HD may confirm hypothesis that CO2 diffusion into the dialysis fluid play a role in hypoventilation and hypoxemia during HD. PaO2 decrease in patients treated by peritoneal dialysis (PD) after infusion 21 of fluid into the peritoneal cavity. Increase in minute ventilation (VE) and oxygen consumption (ViO2) at 2nd and 4rs hour of PD indicate that substrate metabolism during dialysis relates to alternations in ventilation. In all patients before dialysis treatment presence of ventilation disturbances of restrictive typ were demonstrated with decreased vital capacity (VC), reduced maximal ventilation (MBC) and lower one-second forced expiratory volume (FEV1). Residual volume (RV) was significantly higher. After HD we observed a significant increase of total lung capacity (TLC) and decrease of RV, whereas after PD a significant decrease of RV.     

Low seroconversion with hepatitis B vaccination in peritoneal dialysis patients

OBJECTIVE: To compare seroconversion using hepatitis B vaccine between hemodialysis (HD) and peritoneal dialysis (PD) patients. DESIGN: Data on PD patients vaccinated were collected retrospectively for the period 1992 to 1995. The data on HD patients were collected prospectively from 1991 to 1994. SETTING: A university outpatient dialysis center. PARTICIPANTS: All adult patients who received all four doses of hepatitis B vaccine while on dialysis were included (47 PD and 50 HD patients). INTERVENTION: Recombinant hepatitis B vaccine (Engerix), 40 micrograms IM was administered at 0, 1, 2, and 6 months. MAIN OUTCOME MEASURE: Seroconversion was measured after completion of the vaccination series. RESULTS: 74% of the HD patients seroconverted compared to 53% of PD patients (p = 0.03). Older, heavier patients compared to all the other patients had a lower seroconversion rate in both the HD patients (55% vs. 78 %) and PD patients (38% vs. 59%) (p = 0.03). CONCLUSION: The seroconversion rate to recombinant hepatitis B vaccine is lower in patients on PD than on HD for unclear reasons. Further studies are required to determine the etiology of this difference.     

Transfusion and recombinant human erythropoietin requirements differ between dialysis modalities

BACKGROUND: Before the routine use of recombinant human erythropoietin (rHuEpo), patients dialysed by peritoneal dialysis (PD) received fewer blood transfusions than patients on haemodialysis (HD). We compared transfusion practices in these groups now that the use of rHuEpo has become standard, while controlling for variables known to influence anaemia of end-stage renal disease (ESRD). Maintenance rHuEpo doses were also compared. METHODS: Data were examined for 157 HD and 126 PD patients during a 2-year period. Potential confounders included age, gender, albumin, iron deficiency, parathyroid hormone (PTH), underlying renal disease, comorbid illness, renal transplant, dialysis adequacy and duration. An intent-to-treat analysis was used, with sensitivity analyses to account for change in treatment and transplant. RESULTS: Mean haemoglobin (Hb) was not different (10.47 g/dl for HD, 10.71 g/dl for PD; P = 0.45). Mean monthly transfusion rate was higher for HD (0.47 units per month vs 0.19; P < 0.01). More HD patients received at least one transfusion (52.9 vs 40.9%; P < 0.01). The maintenance rHuEpo dose was higher for HD (7370 U/week vs 5790 U/week; P = 0.01). The only factors associated with risk of being transfused were dialysis duration and mode of dialysis (less risk for PD, odds-ratio 0.57; 95% confidence interval 0.35-0.92). CONCLUSIONS: Despite the routine use of rHuEpo, HD patients received more blood and rHuEpo than PD patients to achieve the same Hb. No patient factors were identified to account for this difference. The use of fewer transfusions and less rHuEpo in PD represents an advantage over HD in terms of both cost and safety.     

Substitution of acetic acid for hydrochloric acid in the bicarbonate buffered dialysate

In a multicenter study including 5 dialysis units, blood acetate changes during 4 h dialysis sessions in 141 patients treated with a 4 mM acetate-containing bicarbonate dialysate (ABD) were evaluated and compared to the values of 114 patients using an acetate-free bicarbonate dialysate (AFD). Acetate-free bicarbonate dialysate was delivered by a dialysis machine from the mixing with water for dialysis of a 1/26.2 bicarbonate concentrate, and a 1/35 acid-concentrate in which acetic acid was substituted for hydrochloric acid (Soludia, Fourquevaux, France). This new type of dialysate was routinely in use for 3 years on average (range, from 2 to 5 years). All patients fasted before and during dialysis. Blood samples were withdrawn at the start and at the end of dialysis sessions. The acetate plasma concentration was determined using the acetyl-CoA synthetase enzymatic method (Boehringer, Manheim, Germany). In patients treated with ABD whose predialysis blood acetate levels were in the physiologic range of < or = 100 microM (n = 113), the acetate plasma concentration increased from a predialysis mean value of 22+/-3 microM to a postdialysis mean value of 222+/-11 microM in 88 patients (78% of patients) whereas the acetate plasma concentration changes remained in the range of physiologic values from 21+/-6 to 58+/-7 microM in the other 25 patients. In contrast, patients treated with AFD whose predialysis blood acetate levels were in the physiologic range (n = 108), acetate plasma concentration increased from a predialysis mean value of 49+/-6 microM to 160+/-19 microM in only 13 patients (12% of patients) whereas acetate plasma concentration changes remained in the range of physiologic values of 23+/-2 to 41+/-3 microM in most of the patients of this group. In this study, a significant number of patients, whether receiving standard or acetate-free bicarbonate dialysates, exhibited an extremely high acetate plasma concentration at the start of the dialysis session. Hyperacetatemia was controlled with AFD in patients whose predialysis acetate plasma concentration of 316+/-82 decreased to 55 +/-23 microM (n = 6) at the end of the dialysis session whereas the acetate plasma concentration remained high when the predialysis concentration was 580+/-76 microM, with a postdialysis concentration of 233+/-39 microM (n = 28). It is concluded that in patients whose predialysis blood acetate levels were in the physiologic range, acetate-containing bicarbonate dialysate induces hyperacetatemia whereas postdialysis blood acetate remains in the normal range in such dialysis patients treated with acetate-free dialysate. Chronic hyperacetatemia, which could be found in dialysis patients, is well controlled by dialysis using an acetate-free dialysate.     

Vancomycin elimination during high-flux hemodialysis: kinetic model and comparison of four membranes

Vancomycin clearance was measured in five patients during dialysis with cuprophane (CU), polysulfone (PS), cellulose triacetate (CT), and polyacrylonitrile (PAN) dialyzers. Vancomycin was significantly cleared during routine high-flux (HF) hemodialysis (HD) with the latter three membranes, but not by CU. Postdialytic rebound of serum vancomycin concentrations was noted following HF dialysis, necessitating use of a two-compartment pharmacokinetic model. Measurement of serum vancomycin concentration immediately postdialysis significantly overestimates intradialytic removal, possibly resulting in inappropriate dose adjustment. Vancomycin infusion during HF HD results in significant drug removal during its administration to the patient, complicating the calculation of an adequate dose.     

Variable memory profiles in Parkinson's disease

Thirty-nine patients with Parkinson's disease (PD) were categorized into one of three subgroups using discriminant function analysis and three key indices from the California Verbal Learning Test (CVLT). Patients were classified as having one of three memory profiles: (a) a normal memory profile; (b) a memory profile often observed in patients with Huntington's disease (HD); or (c) a memory profile often observed in patients with Alzheimer's disease (AD). Twenty of the patients with PD were classified as having a normal profile, 10 as having an HD profile, and 9 as having an AD profile. The three subgroups did not differ on measures of global cognitive functioning, letter fluency, confrontation naming, or visuo-construction, suggesting that the patients with PD with an AD memory profile were not experiencing AD, per se. These results demonstrate that the memory deficits associated with PD can be similar to those found in patients with either HD or AD, and argues against the notion that the behavioral manifestations of PD are homogeneous.     

What is the place of peritoneal dialysis in the integrated treatment of renal failure?

The role of peritoneal dialysis (PD) in renal replacement therapy (RRT) remains unclear. There are no controlled trials to provide hard evidence of its efficacy. Comparative studies with haemodialysis from different centres and countries have given conflicting results even when allowing for case mix. Data from the United States on patients starting or receiving treatment in the late 1980s suggested a worse prognosis for older patients, particularly diabetics receiving PD as compared to HD. Analysis of the USRDS data base for patients starting in the early 1990s shows an improvement in outcome but with no difference in overall mortality. The Canadian registry has recently published data showing a better survival with PD than with HD in the first two years of RRT. Morbidity is similar with both therapies, although hospitalization is increased with PD. Unfortunately long-term technique survival is not as good with PD. However, PD has certain medical advantages, particularly the maintenance of residual renal function that contributes to solute and fluid removal. It may also postpone the onset of amyloidosis. Patients transplanted after previous PD have a decreased risk of early acute renal failure and equally good long-term results when compared to those patients who were on HD before transplantation. The quality of life is as good with PD as with center HD, and there are social advantages to PD including an increased chance of employment, more flexible holidays and avoidance of thrice weekly travel to a dialysis center. PD also has logistical advantages and can be utilized by the majority of new patients. We therefore conclude that PD has potential advantages early in the course of RRT, and should therefore be offered as a first option to all suitable new patients. Whether PD has a major or minor role in later years (> 5) remains unclear.     

Is beta-carotene an antioxidant?

The clinical efficacy of s.c. erythropoietin (EPO) injected subcutaneously once weekly was compared in patients (median age of 63 years) on peritoneal dialysis (PD, n = 19) and in haemodialysis (HD, n = 13). The blood haemoglobin prior to start of EPO was not significantly different between the groups. The mean (+/- SD) dose of EPO given to achieve a blood haemoglobin level of 100 g/l was not significantly different between the PD and the HD-responders (85 +/- 45 units/kg body weight and week, versus 112 +/- 33, respectively). Significantly more patients using PD than in HD achieved a haemoglobin level > or = 95 g/l (p = 0.02). The HD group had significantly higher ferritin values. Serum iron and intact PTH were not different between the groups. In conclusion, s.c. EPO injections once, or occasionally twice, weekly increased blood haemoglobin levels in a greater proportion of patients on PD than in those on HD.     

Differential suppression of dialysis patients' lymphocyte IFN-gamma production by glucocorticoids and cyclosporine

IFN-gamma is a potent pro-inflammatory cytokine involved in the immunologic rejection of transplanted organs. Having previously demonstrated differential suppressive effects of methylprednisolone (MP), prednisolone (P) and cyclosporine (CsA) on dialysis patients' lymphocyte proliferative responses to phytohaemagglutinin (PHA), we studied the effects of these drugs on dialysis patients' lymphocyte IFN-gamma production during mitogenic and allogeneic (MLR) stimulation. The mean +/- SEM 50% inhibitory concentration (ng/ml) on cell proliferation was significantly lower for MP than P in PHA-stimulated haemodialysis (HD) patients' (35 +/- 7 vs 152 +/- 25, P < 0.001) and peritoneal dialysis (PD) patients' (35 +/- 11 vs 134 +/- 33, P = 0.001) cultures and in HD patients' MLR cultures (15 +/- 3 vs 48 +/- 9, P < 0.001). The mean +/- SEM fractional responses (PHA or MLR + drug/PHA or MLR) in culture supernatant IFN-gamma concentrations were significantly lower with 10(-7) M concentrations of MP than P in HD (0.19 +/- 0.05 vs 0.31 +/- 0.06, P = 0.01) and PD (0.30 +/- 0.11 vs 0.46 +/- 0.11, P < 0.05) PHA cultures and in HD MLR cultures (0.15 +/- 0.04 vs 0.28 +/- 0.07, P = 0.01). CsA (400 ng/ml) alone not only caused less than 50% inhibition of IFN-gamma production in 15/27 HD PHA, 6/14 PD PHA and 4/13 HD MLR cultures, but actually stimulated it in 9 HD and 5 PD PHA cultures. The results suggest that: (1) MP has greater immunosuppressive potential than P for renal transplant recipients; (2) the stimulation of IFN-gamma by CsA in some patients could be harmful in patients with initial allograft dysfunction; and (3) pre-transplant in-vitro assessment of recipients' PBMC responsiveness to glucocorticoids and CsA may help individualize the post-transplant immunosuppressive regimen.     

The cost of caring for end-stage kidney disease patients: an analysis based on hospital financial transaction records

The costs of care for end-stage renal disease patients continue to rise because of increased numbers of patients. Efforts to contain these costs have focused on the development of capitated payment schemes, in which all costs for the care of these patients are covered in a single payment. To determine the effect of a capitated reimbursement scheme on care of dialysis patients (both hemodialysis [HD] and peritoneal dialysis [PD]), complete financial records (all reimbursements for inpatient and outpatient care, as well as physician collections) of dialysis patients at a single medical center over 1 year were analyzed. For the period from July 1994 to July 1995, annualized cost per dialysis patient-year averaged $63,340, or 9.8% higher than the corrected estimate from the U.S. Renal Data Service (USRDS; $57,660). The "most expensive" 25% of patients engendered 44 to 48% of the total costs, and inpatient costs accounted for 37 to 40% of total costs. Nearly half of the inpatient costs resulted from only two categories (room charges and inpatient dialysis), whereas other categories each made up a small fraction of the inpatient costs. PD patients were far less expensive to care for than HD patients, due to reduced hospital days and lower cost of outpatient dialysis. Care for a university-based dialysis population was only slightly more expensive than estimates predicted from the USRDS. These results validate the USRDS spending data and suggest that they can be used effectively for setting capitated rates. Efforts to control costs without sacrificing quality of care must center on reducing inpatient costs, particularly room charges and the cost of inpatient dialysis.     

Biological basis of hypoalbuminemia in ESRD

Hypoalbuminemia is associated with mortality in patients with end-stage renal disease (ESRD) maintained either on peritoneal dialysis (PD) or hemodialysis (HD). Serum albumin concentration is determined by its rate of synthesis, by the catabolic rate constant (the fraction of the vascular pool catabolized per unit time), by external losses, and by redistribution from the vascular to the extravascular space. Hypoalbuminemia in dialysis patients is primarily a consequence of reduced albumin synthesis rate in both HD and PD patients, and in the case of PD patents, of transperitoneal albumin losses as well. Continuous ambulatory peritoneal dialysis patients are able to increase albumin synthesis to replace losses. Thus, ESRD does not directly suppress albumin synthesis. The rate of albumin synthesis is inversely proportional to the serum concentration of one potential acute phase protein (alpha2 macroglobulin), and albumin concentration is inversely proportional to that of either C-reactive protein or serum amyloid A in both HD and PD patients. The cause of decreased albumin synthesis is primarily a response to inflammation (the acute phase response), although it is possible that inadequate nutrition may also contribute. The cause of the inflammatory response is not immediately evident. There is no evidence that shifts of albumin to the extravascular space or that dilution of the plasma by volume expansion plays any role in causing hypoalbuminemia in ESRD patients.     

Omeprazole attenuates oxygen-derived free radical production from human neutrophils

To look for patients with extreme urea rebound, we drew intradialytic samples one third of the way into dialysis during routine modeling for 3 months. The samples taken postdialysis were obtained after stopping the blood pump, without any slow flow period. Using the Smye equations, the intradialytic urea level was used to predict urea rebound, expressed as Kt/V-equilibrated minus Kt/V-single pool (deltaKt/V). Results were averaged for the 3-month period in 369 patients. Mean estimated deltaKt/V was -0.20 +/- 0.13, which was similar to but slightly higher than the predicted value (-0.6 x K/V + 0.03) of -0.19 +/- 0.04. In 27 patients, extreme rebound (mean deltaKt/V < -0.40) was found. Sixteen of these patients consented to further study, but only after access revision in four patients. In these patients, additional slow flow samples after 15 seconds and 2 minutes of slow flow, respectively, were drawn one third of the way into dialysis and postdialysis, and a sample was drawn 30 minutes after dialysis. On restudy, postdialysis rebound was still high with full flow samples deltaKt/V = -0.40 +/- 25, but was much lower (-0.18 +/- 0.07) and similar to predicted rebound (-0.19 +/- 0.05; P = NS) when based on 15-second slow flow samples. Eight of the 16 had marked (>15%) access recirculation by urea sampling, and deltaKt/V based on full flow post samples correlated with access recirculation (r = -0.91). The results suggest that the Smye method is valuable for identifying patients with aberrantly large postdialysis rebound values. When the postdialysis samples are drawn without an antecedent slow flow period, most patients with extreme rebound values turn out to have marked access recirculation.     

Sulfur mustard-induced microvesication in hairless guinea pigs: effect of short-term niacinamide administration

It has been postulated that sulfur mustard (HD) damage may activate poly(ADP-ribose) polymerase (PADPRP), resulting in depletion of cellular NAD+. This biochemical alteration is postulated to result in blister (vesicle) formation. It has been previously demonstrated that niacinamide (NAM), an inhibitor of PADPRP and a precursor for NAD+ synthesis, may be useful as a pretreatment compound to reduce HD-induced microvesication. The present study was undertaken to determine whether niacinamide's protective action could be extended beyond 24 hr and if the degree of microvesication is related to changes in skin NAD+ content. HD exposures were made by vapor cup to hairless guinea pigs. Niacinamide (750 mg/kg, ip) given as a 30-min pretreatment did not reduce the degree of microvesication 72 hr after HD compared to saline controls. However, niacinamide given as a 30-min pretreatment and at 6-, 24-, and 48-hr after HD, exhibited a 28% reduction in microvesication 72 hr after HD. Skin NAD+ content at 72 hr after HD was depleted by approximately 53% in the saline and NAM-treated groups. Skin NAD+ content was depleted despite NAM administration. Niacinamide did not reduce the degree of erythema at 48 or 72 hr. These results suggest that niacinamide's protective effect against HD-induced microvesication may be extended for at least 72 hr, but NAM levels must be sustained during the post-HD period. The link between maintenance of skin NAD+ and reductions in microvesication is still uncertain.     

A photographic internship in India

Psychotic symptoms among patients receiving hemolytic dialysis (HD) are quite common, while studies showing pharmacokinetics and clearances of neuroleptics in such patients are few. In such instances, previous studies recommended a single administration of neuroleptics with about 1/3 to 1/2 of the normal dose for patients without renal failure. We made a study of 4 cases of delirious patients receiving HD and investigated the relationship between a daily dose of haloperidol (HP), its blood concentration and changes of delirium symptoms before and after HD. Oral or intravenous doses of HP (12-24 mg) were required for the improvement of delirium. Blood concentration increased in proportion to the HP dosage in all patients, and its average was significantly higher than that of the control group. Approximately 25% of clearance was found before and after HD. These studies suggest that the HP dosage for HD patients needs to be larger than previously assumed. Changes in the pharmacokinetics of HP in HD patients seemed to be influenced by a variety of factors such as binding rate with blood serum albumin and HP, metabolic pathway of HP, and sensitivity of HP in the brain.     

Ambulatory blood pressure monitoring in dialysis patients and estimation of mean interdialytic blood pressure

To define blood pressure (BP) patterns and control in dialysis patients, 48-hour ambulatory BP monitoring was performed in 36 hemodialysis and 18 peritoneal dialysis patients. Monitoring began during a dialysis session for hemodialysis patients. Data revealed significantly lower diastolic BP (DBP) and lower diastolic load (percentage of diastolic values > 90 mm Hg) in hemodialysis patients compared with peritoneal dialysis patients (80.6 mm Hg v 88.8 mm Hg, respectively, [P < 0.03] and 26% v 45%, respectively [P < 0.03]) for the 48-hour period. When the 2 days were analyzed separately, the difference in diastolic pressures and loads was significant only for the first (dialysis) day. Similarly, trends toward lower systolic BP (SBP) and systolic load in hemodialysis patients existed throughout monitoring and were greater in magnitude during the first day. BP data were fit to a random-coefficient growth curve model to detect periodicity. This sensitive model did not detect diurnal variation of BP in either group. The incidence of hypotension did not differ between the two groups (2.0% v 1.0% of total observations, hemodialysis v peritoneal dialysis). In the hemodialysis group, the proportion of hypotensive observations was significantly greater during the 4 hours postdialysis compared with other periods (5.6% v 1.6%; P < 0.02), a finding that likely reflects the practice of holding antihypertensives until after hemodialysis. However, patient diaries did not reflect hypotensive symptoms during this time. In the hemodialysis group, mean BP and predialysis BP did not correlate with interdialytic sodium load or weight gain. Predialysis and postdialysis BP (recorded by dialysis nurses) correlated significantly with mean BP. Predialysis SBP overestimated mean SBP by an average of 10 mm Hg, while postdialysis SBP underestimated mean SBP by an average of 7 mm Hg. To create formulas to estimate mean SBP and DBP in hemodialysis patients, multiple linear regression was used to model these variables against age, sex, race, and average prehemodialysis/posthemodialysis BP. The model achieved a high degree of fit (r2 = 0.72 for SBP; r2 = 0.65 for DBP), demonstrating that prehemodialysis and posthemodialysis BP can be used to predict mean BP in hemodialysis patients. In summary, our data show the absence of a diurnal variation of BP in dialysis patients and lower BP in hemodialysis patients compared with peritoneal dialysis patients. Among hemodialysis patients, more hypotension occurred after dialysis compared with other periods, and predialysis and postdialysis BP can be used to model mean BP levels.     

A comparative study of the outcome of renal transplantation in peritoneal dialysis and hemodialysis patients

Fifty-four cases of renal transplantation performed in peritoneal dialysis (PD) patients were compared with 48 cases in hemodialysis (HD) patients. Three immunosuppressive treatments were used: prednisolone, azathioprine and cyclosporine. Methylprednisolone was used to treat rejection, and polyclonal Atgem or monoclonal OKT3 antibodies were used if there was no response. There was no difference in sex, age, donor source, immunosuppressive regime, duration of dialysis before transplantation, or duration of follow-up between the two groups. Following transplantation, there was no significant difference in patient mortality and survival or graft survival between the groups. The incidences of infections were also similar in the two groups. PD is commonly used in developing countries as an alternative to hemodialysis for the treatment of chronic renal failure. This study has shown that renal transplantation can be successfully performed in patients treated by this method.     

Cesarean section rates: effects of participation in a performance measurement project

BACKGROUND: According to previous studies, postdialysis urea rebound (PDUR) is achieved within 30-90 min, leading to an overestimation of Kt/V of between 15 and 40% in 3- to 5-hour dialysis. The purpose of the study was to assess the impact of PDUR on the urea reduction ratio (URR), Kt/V and normal protein catabolic rate (nPCR) with long 8-hour slow hemodialysis. METHODS: This study was performed in 18 patients (13 males/5 females), 62.5 +/- 11.7 years of age, hemodialyzed for 3-265 months. Initial nephropathies were: 3 diabetes; 2 polycystic kidney disease; 3 interstitial nephritis; 2 nephrosclerosis; 3 chronic glomerulonephritis, and 5 undetermined. Residual renal function was negligible. The dialysis sessions were performed using 1- to 1.8-m2 cellulosic dialyzers during 8 h, 3 times a week. Blood flow was 220 ml/min, dialysate flow 500 ml/min, acetate or bicarbonate buffer was used. Serial measurements of the urea concentration were obtained before dialysis, immediately after dialysis (low flow at t = 0), and at 5, 10, 20, 30, 40, 60, 90 and 120 min, and before the next session. The low-flow method was used to evaluate the access recirculation, second-generation Daugirdas formulas for Kt/V, and Watson formulas for total body water volume estimation. The difference between the expected urea generation (UG) and urea measured after dialysis (global PDUR) defines net PDUR (n-PDUR). RESULTS: The n-PDUR usually became stable after 58 +/- 25 (30-90) min. Its mean value was 17 +/- 10% of the 30-second low-flow postdialysis urea (3.9 +/- 2 mmol/l). This small postdialysis urea value and the importance of UG in comparison with shorter dialysis justify the use of n-PDUR. Ignoring n-PDUR would lead to a significant 4% overestimation (p < 0.001) of the URR (79 +/- 7 vs. 76 +/- 8%), 12% of Kt/V (1.9 +/- 0.4 to 1.7 +/- 0.38) and 4% of the nPCR (1.1 +/- 0.3 to 1.05 +/- 0.3). n-PDUR correlated negatively with postdialysis urea (r = 0.45 p = 0.05), positively with URR (r = 0.31 p = 0.01) and Kt/V (r = 0.3 p = 0.03) but not with K, and negatively with the urea distribution volume (r = 0.33 p = 0.05). Mean total recirculation, ultrafiltration rate, predialysis urea levels and urea clearance did not correlate with n-PDUR. CONCLUSION: We found a significant PDUR in long-slow hemodialysis after a mean of 1 h after dialysis. This PDUR has a less important impact upon dialysis delivery estimation than short 3- to 5-hour hemodialysis, especially for the lower Kt/V or URR ranges. This is explained by the low-flux, high-efficiency, and long-term dialysis. Its inter-individual variability incites us to calculate PDUR on an individual basis.     

Signal averaged electrocardiography (SAECG) in patients on hemodialysis

Cardiovascular diseases are the major cause of mortality in patients on hemodialysis (HD). Recently, signal averaged electrocardiography (SAECG) has been developed to detect ventricular late potentials (LP) noninvasively from the body surface for identifying patients at sudden death or ventricular tachycardia. We performed SAECG in 42 patients before and after HD. As a result, postdialysis total filtered QRS duration (FQRS) was significantly increased compared with predialysis FQRS. Postdialysis duration of low amplitude signal under 40 microV in the latter part of QRS (LAS40) tended to increase compared with predialysis LAS40. Before HD, there were no patients with LP and only one patient (2.4%) with abnormal SAECGs. In contrast, after HD, there were three patients (7.1%) with LP and three more patients (7.1%) with abnormal SAECGs. Furthermore, there was a significant correlation between the changes in LAS40 (delta LAS40) and those in potassium (K) (delta K) during HD. We further examined the relation between LAS40 and the concentration of K, by comparing the correlation coefficient between patients in the high-K group (predialysis K > or = 5.0 mEq/L; 20 patients) and those in the low-K group (predialysis K < 5.0 mEq/L; 22 patients). In the low-K group, there was no significant correlation between delta LAS40 and delta K. However, in the high-K group, there was a significant correlation between delta LAS40 and delta K. In conclusion, SAECG indices worsened during HD, and an insufficient decrement of serum potassium by HD is suggested to have been an arrhythmogenic factor in the high-K group.     

Oral ganciclovir dosing in transplant recipients and dialysis patients based on renal function

BACKGROUND: An oral formulation of ganciclovir (GCV) was recently approved for the prevention of cytomegalovirus disease in solid organ transplant recipients. This study was designed to determine the bioavailability of GCV and to test a dosing algorithm in transplant and dialysis patients with different levels of renal function. METHODS: Pharmacokinetic studies were carried out in 23 patients who were either a recipient of an organ transplant or on hemodialysis. Drug dosing was established by the following algorithm based on calculated creatinine clearance (CrCl): CrCl = [(140-age) x body weight]/(72 x Cr) x 0.85 for women that is, CrCl >50 ml/min, 1000 mg every 8 hr; CrCl of 25-50 ml/min, 1000 mg every 24 hr; CrCl of 10-24 ml/ min, 500 mg every day; CrCl < 10 ml/min (or on dialysis), 500 mg every other day after dialysis. GCV was taken within 30 min after a meal. The patients received oral GCV for between 12 days and 14 weeks. Serum specimens (or plasma from patients on hemodialysis) obtained at steady state were analyzed for GCV concentrations by high-performance liquid chromatography. In nine of the transplant recipients, absolute bioavailability was determined by comparing GCV levels after single oral and intravenous doses of GCV. RESULTS: The following GCV concentrations (mean +/-SD) were determined: with CrCl of > or =70 ml/min, the minimum steady-state concentration (Cmin) and maximum concentration (Cmax) were 0.78+/-0.46 microg/ml and 1.42+/-0.37 microg/ml, respectively, with a 24-hr area under the concentration time curve (AUC0-24) of 24.7+/-7.8 microg x hr/ml; with CrCl of 50-69 ml/min, the Cmin and Cmax were 1.93+/-0.48 and 2.57+/-0.39 microg/ml, respectively, with an AUC0-24 of 52.1+/-10.1 microg x hr/ml; with CrCl of 25-50 ml/min, the Cmin and Cmax were 0.41+/-0.27 and 1.17+/-0.32 microg/ml, respectively, with an AUC0-24 of 14.6+/-7.4 microg x hr/ml. For one patient with a CrCl of 23.8 ml/min, the Cmin and Cmax were 0.32 and 0.7 microg/ml, respectively, with an AUC0-24 of 10.7 microg x hr/ml. With CrCl of <10 ml/min, the mean Cmin and Cmax were 0.75+/-0.42 and 1.59+/-0.55 microg/ml, respectively, with a mean AUC0-24 of 64.6+/-18.8 microg x hr/ml. Absolute bioavailability, for the nine patients so analyzed, was 7.2+/-2.4%. For those patients with end-stage renal failure, GCV concentrations fell during dialysis from a mean of 1.47+/-0.48 microg/ml before dialysis to 0.69+/-0.38 microg/ml after dialysis. CONCLUSIONS: The bioavailability of oral GCV in transplant patients was similar to that observed in human immunodeficiency virus-infected patients. However, levels between 0.5 and 1 microg/ml (within the IC50 of most cytomegalovirus isolates) could be achieved with tolerable oral doses. The proposed dosing algorithm resulted in adequate levels for patients with CrCl greater than 50 ml/min and for patients on dialysis. For patients with CrCl between 10 and 50 ml/min, the levels achieved were low and these patients would likely benefit from increased doses.